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Slow brushing over the skin activates C-tactile nerve fibers that transmit pleasant tactile experiences in healthy subjects, leading to an inverted U-shaped velocity dependence of ratings: C-tactile optimal stroking stimulations are rated as more pleasant than slower or faster stimulations. Chronic pain diseases such as postherpetic neuralgia (PHN) and complex regional pain syndrome show altered C-fiber innervation density, sensory loss, and pain sensitization.
Evidence supports but is inconclusive that sensitization contributes to chronic pain in some adults with sickle cell disease (SCD). We determined the prevalence of pain sensitization among adults with SCD pain compared with pain-free healthy adults. In a cross sectional, single session study of 186 African American outpatients with SCD pain (age 18-74 years, 59% female) and 124 healthy age, gender, and race matched control subjects (age 18-69 years, 49% female), we compared responses to standard thermal (Medoc TSA II) and mechanical stimuli (von Frey filaments). Although we observed no significant differences in thermal thresholds between controls and patients, patients with SCD had lower pain thresholds to mechanical stimuli and reported higher pain intensity scores to all thermal and mechanical stimuli at a non-painful body site. Compared with controls, about twice as many patients with SCD showed sensitization: 12% versus 23% at the anterior forearm site (p=.02), and 16% versus 32% across three tested sites (p=.004). Among patients with SCD, 18% exhibited some element of central sensitization. Findings indicate that persistent allodynia and hyperalgesia can be part of the SCD pain experience and should be considered when selecting therapies for SCD pain. Perspective: Compared with matched healthy controls, quantitative sensory testing in adults with pain and sickle cell disease (SCD) demonstrates higher prevalence of sensitization, including central sensitization. The findings of allodynia and hyperalgesia may indicate neuropathic pain and could contribute to a paradigm shift in assessment and treatment of SCD pain.
Evidence from genome-wide and candidate gene association studies, familial aggregation and linkage analyses demonstrate the genetic contribution to fibromyalgia (FM) disease. This study aimed to identify genetic biomarkers of FM and its related comorbid disorders, by exploring 41 polymorphisms potentially involved in FM pathogenesis in families with at least one patient with FM.
Cognitive-behavioral therapy (CBT) is effective for pediatric chronic pain, but little is understood about which youth are most likely to benefit. The current study aimed to identify individual characteristics for which CBT yielded the greatest (and least) clinical benefit among adolescents with chronic pain participating in a multi-center randomized controlled trial (RCT) of internet-delivered CBT (WebMAP2). A total of 273 adolescents ages 11-17 with chronic pain (Mage=14.7; 75.1% female) were randomly assigned to internet-delivered CBT or internet-delivered pain education and evaluated at pre-treatment, post-treatment, and two longer-term follow-up periods (6 and 12 months). Multi-level growth models tested several adolescent- and parent-level moderators of change in pain-related disability including (1) adolescent age, sex, pain characteristics, distress, and sleep quality and (2) parent education level, distress, and protective parenting behaviors. Young adolescents (ages 11-14 vs. older adolescents ages 15-17) and those whose parents experienced lower levels (vs. higher levels) of emotional distress responded better to internet CBT treatment, showing greater improvements in disability up to 12 months post-treatment. This study expands knowledge on who benefits most from internet-delivered psychological treatment for youth with chronic pain in the context of a large multicenter RCT, suggesting several avenues for maximizing treatment efficacy and durability in this population. Perspective: This study identified adolescent- and parent-level predictors of treatment response to Internet-based CBT for pediatric chronic pain up to 12 months later. Younger adolescents and those whose parents had lower levels of distress may particularly benefit from this intervention. Older adolescents and those whose parents exhibit higher distress may require alternative treatment approaches.
Opioid-induced hyperalgesia (OIH) is a phenomenon whereby opioids increase patients' pain sensitivity, complicating their use in analgesia. We explored practitioners' attitudes towards, and knowledge concerning diagnosis, risk factors, and treatment of OIH.
Small fibre neuropathy is a common pain disorder, which in many cases fails to respond to treatment with existing medications. Gain-of-function mutations of voltage-gated sodium channel Nav1.7 underlie dorsal root ganglion neuronal hyperexcitability and pain in a subset of patients with small fibre neuropathy. Recent clinical studies have demonstrated that lacosamide, which blocks sodium channels in a use-dependent manner, attenuates pain in some patients with Nav1.7 mutations; however, only a subgroup of these patients responded to the drug. Here, we used voltage-clamp recordings to evaluate the effects of lacosamide on five Nav1.7 variants from patients who were responsive or non-responsive to treatment. We show that, at the clinically achievable concentration of 30 μM, lacosamide acts as a potent sodium channel inhibitor of Nav1.7 variants carried by responsive patients, via a hyperpolarizing shift of voltage-dependence of both fast and slow inactivation and enhancement of use-dependent inhibition. By contrast, the effects of lacosamide on slow inactivation and use-dependence in Nav1.7 variants from non-responsive patients were less robust. Importantly, we found that lacosamide selectively enhances fast inactivation only in variants from responders. Taken together, these findings begin to unravel biophysical underpinnings that contribute to responsiveness to lacosamide in patients with small fibre neuropathy carrying select Nav1.7 variants.
There are insufficient studies providing Minimal Clinically Important Difference (MCID) for outcomes related to temporomandibular disorders (TMD).
To investigate and compare the safety and the pharmacokinetics of dihydroergotamine (DHE) after administration of intranasal DHE powder (STS101), intranasal DHE spray (Migranal ), and intramuscular (IM) DHE injection in healthy subjects.
Osteoarthritis (OA) is known to be a slowly progressive disease that alters all tissue compartments of the joint involved with a characteristic degradation of the cartilage, bone remodeling, and inflammation. One of the prominent symptoms in OA patients is pain, but a few radiological, inflammatory or structurally related biomarkers have shown little if any associations to pain. This study aimed to assess serum levels of 92 markers involved in inflammatory pathways in patients with knee OA (KOA) and evaluate their possible associations with the clinical pain intensity.